Acoustic methods for estimating structural properties of soft tissues are proposed. Two long-term research objectives are identified: discover the major sources of scattering in tissues, and use that information to detect, grade, and follow the progress of disease. Towards these objectives, we propose five Specific Aims over three years. The first three aims emphasize measurements of basic acoustic properties of tissues necessary to interpret clinical findings. Our first aim is to measure and model correlation functions that describe backscattered ultrasound in kidney and liver tissues. Accurate correlation models are necessary to measure backscatter coefficients and therefore scatterer size and scattering strength values accurately. The effects of an inhomogeneous propagation path and blood perfusion on acoustic measurements is the subject of aim 2, where the relationship between in vitro and in situ measurements is investigated. In aim 3, we study the contributions of collagen, lipid, and water to measurements of acoustic properties in tissues. Biochemical assays and stereological morphometric techniques will be used to find relationships between the composition and structure of tissue and acoustic measurements. The last two aims are designed to discover and develop the clinical potential of the techniques. The intent of aim 4 is to measure acoustic properties of normal kidneys in vivo, and observe well-defined changes in renal structure in patients. In aim 5, our methods will be implemented on a state-of-the-art imaging system, which allows us use the advantages of transducer array technology, and explore the potential for high-speed parametric imaging. In all, the proposal is an effort to encompass a significant range of factors important for evaluating the potential of quantitative ultrasound as a noninvasive diagnostic alternative. Our immediate goal is to offer a tool for probing soft tissue microstructure that will eventually provide a safe and effective alternative to serial biopsy. Our long-range goal is to exploit quantitative ultrasound as a tool for identifying, in vivo, the sources of soft tissue scattering, improving the detection of early changes in tissues that accompany the presence of disease, providing a probe to study disease mechanisms, and aiding in the design of new imaging systems that can be optimized for specific tasks.